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Induction of myeloma-specific cytotoxic T lymphocytes ex vivo by CD40-activated B cells loaded with myeloma tumor antigens

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Abstract

We investigated to establish CD40-activated B cells (CD40-B cells) as alternative antigen-presenting cells (APCs) for the induction of myeloma-specific cytotoxic T lymphocytes (CTLs). To generate CD40-B cells, peripheral blood mononuclear cells were co-cultured with CD40L-transfected J558 cells in the presence of IL-4, insulin, transferrin, and cyclosporine for 14 days, and pulsed with myeloma lysates. The CD40-B cells consistently expressed high levels of CD80, CD86, CD54, CCR7, and HLA-DR. The CD40-B cells produced IL-12, IFN-γ, and IL-6 during the culture period, but not IL-10. In addition, the CD40-B cells showed potent allogeneic T-cell stimulatory capacities that depended on the dose ratio and had the potential to polarize naïve T cells into Th1 subsets. The CD40-B cells loaded with tumor lysates induced strong target-specific CTLs, based on large numbers of IFN-γ secreting cells and higher cytotoxic activity against target cells compared to the CD40-B cells without the tumor lysates. These results suggest that CD40-B cells loaded with myeloma lysates might provide alternative APCs for cellular immunotherapy in patients with myeloma.

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Acknowledgements

This research was supported by grant no. RTI05-01-01 from the Regional Technology Innovation Program of the Ministry of Commerce, Industry and Energy (MOCIE), Republic of Korea, and by a grant of the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A080489).

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Authors and Affiliations

  1. Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeonnam, South Korea

    Sang-Ki Kim, Thanh-Nhan Nguyen Pham, Tuyet Minh Nguyen Hoang, Hyun-Kyu Kang, Chun-Ji Jin, Jong-Hee Nam, Ik-Joo Chung & Je-Jung Lee

  2. Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, South Korea

    Sang-Ki Kim

  3. Department of Hematology–Oncology, Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, South Korea

    Thanh-Nhan Nguyen Pham, Tuyet Minh Nguyen Hoang, Hyun-Kyu Kang, Deok-Hwan Yang, Yeo-Kyeoung Kim, Ik-Joo Chung, Hyeoung-Joon Kim & Je-Jung Lee

  4. Department of Surgery, Chonnam National University Medical School, Gwangju, South Korea

    Chun-Ji Jin, Sang-Young Chung & So-Jin-Na Choi

  5. The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, South Korea

    Thanh-Nhan Nguyen Pham, Hyun-Kyu Kang, Chun-Ji Jin, Jong-Hee Nam, Sang-Young Chung, So-Jin-Na Choi, Ik-Joo Chung & Je-Jung Lee

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  1. Sang-Ki Kim
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Correspondence to Je-Jung Lee.

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Sang-Ki Kim and Thanh-Nhan Nguyen Pham equally contributed to this work.

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Kim, SK., Nguyen Pham, TN., Nguyen Hoang, T.M. et al. Induction of myeloma-specific cytotoxic T lymphocytes ex vivo by CD40-activated B cells loaded with myeloma tumor antigens. Ann Hematol 88, 1113–1123 (2009). https://doi.org/10.1007/s00277-009-0721-y

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